Search PubMed⌕ Search

Biomedical subjects

D Brooks

Publications and source records attributed to D Brooks.

At least 73 records · Page 4Linked to original sources
PubMed1997

Ventilatory and arousal responses to hypoxia and hypercapnia in a canine model of obstructive sleep apnea.

We have previously described a canine model of obstructive sleep apnea (OSA) in which sleep-wake state is monitored continuously by a computer that produces tracheal occlusion when sleep occurs. Our aim was to assess the effects of long-term application of this model on resting ventilation and on the ventilatory and arousal responses to hypercapnia and hypoxia. Five dogs were maintained on the model for 15.5 +/- 1.7 (mean +/- SE) wk, with a mean apnea index of 57.5 +/- 4.5 occlusions/h of sleep. Resting ventilation and the ventilatory and arousal responses to progressive hypoxic and hypercapnic rebreathing were assessed during wakefulness (W) and both slow-wave (SWS) and rapid-eye-movement (REM) sleep at baseline prior to intervention, at the end of the OSA phase, and following a 1 to 3-mo recovery period. During the period of OSA there were small changes in respiratory timing at rest, but no significant changes in PCO2 or SaO2. As compared with baseline, the ventilatory response to hypoxia during OSA was strikingly reduced during W, and significantly although less markedly reduced during SWS and REM. The reduction was due to a decreased breathing frequency response to hypoxia. In addition, during OSA there was a significant decrease from baseline in SaO2 at arousal during hypoxic rebreathing in both SWS and REM. All responses returned to normal during recovery. In contrast to hypoxia, hypercapnic ventilatory responses during OSA were slightly increased over their baseline values both in W and SWS, owing to a leftward shift of the ventilation-versus-PCO2 relationship. During recovery, these responses reverted partly to baseline for W and reverted completely to baseline for SWS. There were no significant changes in arousal PCO2 during hypercapnic rebreathing in either SWS or REM across the pre-OSA baseline, OSA, and post-OSA recovery periods. We conclude that long-term application of the OSA model is associated with a selective, reversible decrease in ventilatory and arousal responses to hypoxia.

Animals↗
PubMed1997

The pharmacokinetics of a single intramuscular dose of amikacin in red-tailed hawks (Buteo jamaicensis).

The pharmacokinetic parameters of amikacin were determined in red-tailed hawks (Buteo jamaicensis) following the i.m. administration of a single 20 mg/kg dose. After a rapid absorption phase, mean amikacin serum concentrations peaked at 65 +/- 12 micrograms/ML 30-45 min following injection. The serum amikacin concentrations decreased to 2.3 +/- 2 micrograms/ml at 12 hr postinjection. Amikacin was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.02 +/- 0.63 hr. The volume of distribution was estimated to be 0.28 +/- 0.03 L/kg. Forty-two isolates of gram-negative bacteria and coagulase-positive Staphylococcus species were cultured from birds of prey presented to the Veterinary Medical Teaching Hospital at the University of California-Davis. The minimum inhibitory concentration (MICs) of amikacin ranged from 0.5 to 8.0 micrograms/ml (mean = 2.5 micrograms/ml). The 20 mg/kg dose used in this study resulted in serum concentrations at or above the MICs for > 12 hr for most of the isolates examined. The heaviest birds had the lowest peak serum amikacin concentrations, and the lightest birds had the highest, despite exact volume replacement for each sample drawn. This observation suggests that doses should be based on factors other than weight alone. Amikacin administered at 15-20 mg/kg/day, either as a single dose or divided into two or three doses, is effective in treating sensitive pathogens of the red-tailed hawk.

Amikacin↗
PubMed1997

Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials.

The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has revealed low interrater reliability in some items and redundancy in others. In view of these shortcomings, we have structured a new scale that includes a zero-to three-point scale for each item in the evaluation of PD. The mental axis includes memory, thought disorders, and depression. Activities of daily living (ADL) includes eight items: speech, eating, feeding, dressing, hygiene, handwriting, walking, and turning in bed. The motor examination includes eight items: speech, tremor, rest and posture, rigidity, finger tapping, arising from chair, gait, and postural stability. Complications of therapy were also included: dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by history. In addition, a global scoring for motor fluctuations that should complement the Hoehn and Yahr Scale was incorporated. In this report, we present a statistical analysis of the ADL, motor evaluation, and complications of therapy sections. Concerning the interrater reliability mean, Kendall's W values were >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES). Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine items of the UPDRS. The mean interrater reliability for both scales across all seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no statistical differences between the scales. Spearman's correlations between items of both scales were significant. Factor analysis of the SPES and UPDRS data revealed a four-factor solution that explained approximately 60% of the data. All participating centers found the SPES easier to apply and quicker to complete, when compared with the UPDRS. The results obtained strongly favor the introduction of SPES for clinical practice.

Activities of Daily Living↗
PubMed1996

Is urine leukocyte esterase test a useful screening method to predict Chlamydia trachomatis infection in women?

We evaluated the use of the leukocyte esterase test (LET) on first-catch urine specimens from women as a screening test to predict infection with Chlamydia trachomatis. For diagnosis, we used Abbott's ligase chain reaction (LCR) on urine specimens and isolation by tissue culture (TC) on cervical brushes. Of 4,053 women attending sexually transmitted disease and family planning clinics, 4.3% (n = 174) were positive by TC and 5.9% (n = 239) were positive by LCR. When LET was compared to TC, the sensitivity, specificity, positive predictive value, and negative predictive value were 54.0, 67.0, 6.8, and 97.0%, respectively. The corresponding performance of LET versus LCR was 53.1, 67.3, 10.1, and 95.8%. Almost half of the laboratory-confirmed chlamydial infections were negative by LET. The low specificity probably reflects multiple causes of pyuria in women and results in a low positive predictive value. LET is neither sensitive nor specific as a predictor of chlamydial infection and cannot be recommended for use as a screening test for C. trachomatis with first-catch urine samples from females from low- or moderate-prevalence populations.

Chlamydia Infections↗
PubMed1996

Validation of a telemetry system for long-term measurement of blood pressure.

We have used an implanted telemetry system to continuously monitor blood pressure (BP) in three dogs for durations ranging from 28 to 75 wk after implantation. Measurements of BP obtained by telemetry were compared every 3-12 wk, with measurements of BP recorded with a manometer-tipped catheter that was inserted into a femoral artery. Over a wide range of both physiological and pharmacologically manipulated pressures (40-200 mmHg), the values of BP obtained by the two methods were highly correlated (all r > 0.966; all P < or = 0.0001). However, the mean differences between the values obtained by the two systems were different from zero (range +29.6 to -1.5 mmHg; P < or = 0.0001), indicating an offset in the BP values recorded from the implanted system. Furthermore, this offset was dependent on the absolute level of the BP. The findings indicate that, for a period of at least 28 wk and up to 75 wk after implantation, the telemetry system accurately measures acute changes in BP and can reliably measure absolute BP provided that the system is properly validated.

Animals↗
PubMed1996

Pharmacokinetic properties of several novel oligonucleotide analogs in mice.

Biophysical and pharmacokinetic properties of five analogs of ISIS 3082, a 20-mer phosphorothioate oligodeoxynucleotide that inhibits the expression of mouse intercellular adhesion molecule 1, were evaluated. Compared to the parent compound, ISIS 3082, the 2'-propoxy modified phosphodiester, ISIS 9044 and the 2'-propoxy phosphorothioate, ISIS 9045, had greater affinity for complementary RNA and were more lipophilic. A chimeric oligonucleotide comprised of 2'-propoxy diester wings and a phosphorothioate deoxy center (ISIS 9046) had equal affinity. It was also more lipophilic than ISIS 3082, but less so than the other 2'-propoxy modified analogs. The two analogs with 5'-lipophilic conjugates, ISIS 9047 (5'-octadecylamine) and ISIS 8005 (5'-(2'-O-hexylamino-carbonyl-oxycholesterol) were more lipophilic than ISIS 3082 (3- and 7-fold, respectively) but had similar affinity for complementary RNA. Binding of ISIS 3082 to bovine serum albumin was salt-dependent and, at physiological concentration (320 mOsmol), the dissociation constant (Kd) was 140 microM. Similarly, the 2'-propoxy phosphodiester, ISIS 9044, displayed salt-dependent bovine serum albumin binding, but not binding was measurable at physiological salt conditions. In contrast, the more lipophilic phosphorothioate analogs displayed much higher affinity to bovine serum albumin at 320 mOsmol than ISIS 3082. After bolus injection to mice, the initial volumes of distribution of the more lipophilic phosphorothioate analogs, ISIS 9045, ISIS 9047 and ISIS 8005, were less and the initial clearance from plasma was slower than ISIS 3082. The pharmacokinetics of the other analogs was similar to ISIS 3082. Distribution of ISIS 3082 into peripheral tissues was similar to that reported for other phosphorothioates with liver and kidney accumulating the highest fraction of the dose. The only modification to markedly influence distribution was the very lipophilic cholesterol conjugate (ISIS 8005), which increased substantially the fraction of the dose accumulated by the liver. Little intact drug was found in urine or feces for any analog, and the patterns of metabolites suggested that for all analogs the principal metabolic pathway was due to 3'-exonuclease activity. The metabolism of ISIS 3082 was similar to that reported for other phosphorothioates. After 2 hr, most of the radioactivity in plasma represented metabolites but, in tissues, intact ISIS 3082 was present for much longer periods of time and metabolites accumulated more slowly. The 24-hr exposure to ISIS 3082 of liver and kidney was 20.7 and 67.9 microM/hr, respectively. The rates of metabolism in plasma, liver and kidney of the two 5'-conjugates, ISIS 9047 and ISIS 8005, were similar to ISIS 3082, as was the pattern of metabolism. The rate of metabolism of ISIS 9044 (2'-propoxy phosphodiester oligonucleotide) was much more rapid in liver and plasma, but surprisingly much slower in the kidney. ISIS 9045 (full 2-propoxy phosphorothioate) was much more stable than ISIS in all tissues, the enhanced stability of ISIS 9045 resulted in increased exposure of liver and kidney to the drug, whereas the exposure of the liver to the two more lipophilic analogs, ISIS 9047 and ISIS 8005, was greater because a higher fraction of the dose was distributed to the liver. The exposure of the kidney to ISIS 9044 was also greater than that to ISIS 3082 due to the surprising stability of the drug in the kidney.

Animals↗
PubMed1996

Nonpeptide endothelin receptor antagonists. VII: Binding characteristics of [3H]SB 209670, a novel nonpeptide antagonist of endothelin receptors.

The data presented in this manuscript describes the binding characteristics of [3H]SB 209670, a potent nonpeptide tritium-labeled endothelin (ET) receptor antagonist. The binding of this antagonist to cloned human ETA and ETB receptors was specific, saturable and of high affinity. The apparent dissociation constants were 0.20 and 1.0 nM for ETA and ETB receptors, respectively. The maximum binding was 4.7 and 22.5 pmol/mg protein for ETA and ETB receptors, respectively. Unlike [125]ET-1, the binding of [3H]SB 209670 was reversible. The half-times (T1/2) for dissociation of this ligand from ETA and ETB receptors were approximately 60 and 10 min, respectively. Competition binding studies using [3H]SB 209670 and unlabeled agonists ET-1, ET-3 and S6c indicated that these agonists displayed similar affinities for human ETB receptors, whereas with ETA receptors, ET-1 was approximately 50-fold and 1500-fold more potent than ET-3 and S6c, respectively. Of the peptide antagonists tested, BQ123 (ETA-selective peptide antagonist), displayed Ki values of 40 and > 2300 nM for ETA and ETB, whereas RES701 (ETB-selective antagonist) displayed Ki values of > 1600 and 81 nM for ETA and ETB receptors, respectively. The nonselective peptide antagonist, PD 142893, was approximately 2-fold more potent for ETA compared with ETB receptors. Similar observations were made with nonselective nonpeptide antagonists, Bosentan, (+/-) SB 209670, SB 209670, and (-) SB 209670. All these compounds were 2 to 10 times more potent for ETA than ETB receptors.

Animals↗
PubMed1995

In vivo delivery of human alpha-L-iduronidase in mice implanted with neo-organs.

Mucopolysaccharidose type I is a lysosomal storage disease caused by a deficiency in the enzyme alpha-L-iduronidase (IDUA). The existence of a secretory pathway for lysosomal enzymes and the capture of secreted molecules by distant cells through binding to mannose-6-phosphate receptors have provided a rationale for enzyme replacement therapy in lysosomal storage diseases. We have used genetically modified fibroblasts implanted into neo-organs as an in vivo delivery system for IDUA. The human IDUA cDNA was isolated and inserted into a retroviral vector where it was expressed from the phosphoglycerate kinase 1 gene promoter. MPS I fibroblasts transduced with this vector showed high levels of IDUA activity and secreted phosphorylated molecules that could be internalized by naive deficient cells. Neo-organs containing 2 x 10(7) IDUA-secreting cells were implanted into nude mice. Human and murine IDUA activities were measured in the liver and spleen of animals sacrificed 35-77 days after implantation. Human IDUA activity corresponded to 0.6-2.3% of the murine enzyme activity in the liver and to 0.1-0.3% in the spleen. These data indicated that human IDUA was secreted from neo-organs and internalized in distant tissues.

Animals↗
PubMed1995

Physical therapy management of the subluxated wrist in children with arthritis.

Arthritis commonly affects the hand and wrist in children and may contribute to loss of range of motion and force of the muscles surrounding the involved joints. The purpose of this case report is to describe a physical therapy protocol for managing a subluxated wrist in children with arthritis. Measures of range of motion and force of the wrist observed in two patients up to 2 years after the implementation of this protocol are also reported. The initial phase of the physical therapy program focused on realigning the subluxated wrist. Heat was used to manage flexor muscle tightness and increase tissue extensibility. The carpal bones were then realigned manually and supported in position with a cast for a period of 72 hours. Once alignment of the wrist was achieved, the emphasis of physical therapy was placed on increasing range of motion and force at the wrist joint through visits to the physical therapist and an extensive home program. Measurements of passive range of motion and active range of motion using a goniometer, grip forces using a modified sphygmomanometer, and peak torque of the wrist extensors using a dynamometer (measured in one patient) were recorded before and up to 2 years following the implementation of the protocol. There was an increase in wrist extension passive range of motion (35 degrees in both patients) and active range of motion (15 degrees in patient 1 and 25 degrees in patient 2) between the measurements obtained before and 1 to 2 years following the implementation of the protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Interrater reliability of auscultation of breath sounds among physical therapists.

BACKGROUND AND PURPOSE: Although auscultation is routinely used in the assessment of respiratory status, the ability of the rater to accurately and consistently identify lung sounds has been questioned. The literature on this issue is sparse and has focused on reliability of auscultation of tape-recorded rather than in vivo lung sounds. The purposes of this study were to determine the interrater reliability of physical therapists in the direct auscultation of lung sounds based on their clinical experience in chest physical therapy and to determine whether the adoption of standardized nomenclature and education on proper technique and interpretation affects reliability. SUBJECTS AND METHODS: A group of 57 registered physical therapists were stratified by clinical experience into four groups. Sixteen therapists (ie, 4 in each stratum) were randomly chosen using a random number table. The following criteria were developed to delineate clinical experience. Group 1 subjects were senior chest physical therapists with at least 5 years of experience in this area of practice. Group 2 subjects were experienced therapists who had a minimum of 2 years of experience in chest physical therapy and were currently practicing in this area. Group 3 subjects were experienced physical therapists in other areas who were also practicing in chest physical therapy on occasional weekend service. Group 4 subjects were new graduates. Ten patients were evaluated by each group of 4 physical therapists using a teaching stethoscope with one diaphragm/bell and four pairs of earpieces. The education session consisted of discussion of the adoption of standardized nomenclature and education on proper technique and interpretation of auscultation. Interrater reliability was assessed before and after the education session using kappa (kappa) values. Comparisons were made between kappa values before and after the education session to determine the effect of education and between groups to determine the effect of clinical experience. RESULTS: The kappa values before the education session were low, indicating poor reliability in detecting specific abnormal sounds (kappa = -.02-.59). Group 1 (seniors in respiratory therapy) and group 4 (new graduates) demonstrated the greatest reliability levels. The lowest kappa values were observed for detecting and categorizing the quality of breath sounds (normal, absent, bronchial, or decreased) (kappa = -.02-.25). Following the education session, there was a general improvement in reliability (kappa = -.30-.77), especially for group 3 (specialists in other areas). The most improvement was noted for the detection of the quality of breath sounds (kappa = .08-.50). CONCLUSION AND DISCUSSION: Reliability of auscultation was poor to fair, in general, before the education session. There was a definite improvement in reliability after the education session. There was no clear effect of clinical experience on reliability, and the agreement among observers appeared to depend on the abnormal lung sound present. Limitations of this study and recommendations for future research are discussed. [Brooks D, Thomas J. Interrater reliability of auscultation of breath sounds among physical therapists.

Auscultation↗
PubMed1995

Respiratory-related heart rate variability persists during central apnea in dogs: mechanisms and implications.

The aim of this study was to determine the mechanism(s) responsible for the persistence of respiratory sinus arrhythmia (RSA) during central apnea. In five awake dogs, heart rate (HR) was recorded during constant mechanical ventilation (MV) and during central apneas produced by cessation of MV. For each of 10 control ventilator cycles before MV was stopped, instantaneous HR was plotted against the time from the onset of lung inflation; the fundamental and first harmonic of a sine wave (at the ventilator frequency) was then fitted to the HR data. For the control cycles, the mean r2 from the curve fits was 0.57 +/- 0.07, showing that a significant component of the HR variability was linked to the ventilator cycle. After MV was stopped, RSA persisted and only by the third "phantom" ventilator cycle during apnea had the degree of fit consistently decreased compared with control dogs (P < 0.02). The persistence of ventilator-linked RSA at the onset of central apnea supports the concept of a "memory" in the respiratory system. Toward the end of central apnea, HR variability reappeared and had the periodicity and rhythmic profile of RSA on 81% of occasions. The presence of RSA-like activity toward the end of central apnea suggests that subthreshold rhythmic respiratory-related activity may be present even before the onset of detectable lung volume changes.

Animals↗
PubMed1995

Immediate effects of arousal from sleep on cardiac autonomic outflow in the absence of breathing in dogs.

To determine the immediate effects of arousal from non-rapid-eye-movement (non-REM) sleep on cardiac sympathetic and parasympathetic activities, six dogs were studied breathing through an endotracheal tube inserted into a chronic tracheostomy. Mean heart rates (HRs) during non-REM sleep were compared with 1) awake periods immediately after spontaneous arousals (ARs) and 2) later periods of stable relaxed wakefulness (RW). During spontaneous breathing, HR increased after AR (mean = 31.0%; P < 0.001) and in RW (mean = 7.6%; P < 0.001). To avoid the confounding influence of changes in breathing pattern, lung volume, and blood gases accompanying AR on HR, further studies were performed during constant mechanical hyperventilation that eliminated spontaneous breathing. In this condition, HR still increased after AR (mean = 29.9%; P < 0.001) and in RW (mean = 5.7%; P < 0.001), suggesting that the HR increases could be mediated by an effect of the state change per se on autonomic activity. This interpretation was confirmed when the HR increases were essentially abolished by combined cardiac sympathetic and parasympathetic block. In contrast, parasympathetic block alone did not prevent the HR increases after AR (mean = 12.2%; P < 0.001) or in RW (mean = 12.3%; P < 0.001), whereas sympathetic block alone almost abolished the HR increases in RW (mean = 3.6%) but did not prevent the HR increases during AR (mean = 30.2%; P < 0.001). The results show that, compared with non-REM sleep, AR is associated with acute cardiac sympathetic activation and parasympathetic withdrawal, whereas stable RW is associated mainly with sympathetic activation. These effects may have clinical relevance to the cardiovascular sequelae of breathing disorders that cause repetitive arousals from sleep.

Animals↗
PubMed1995

Chest physical therapy management of patients with cystic fibrosis. A meta-analysis.

The purpose of this overview is to quantitatively assess the conflicting body of literature concerning the efficacy of physical therapy modalities for clearing bronchial secretions in the treatment of patients with cystic fibrosis (CF). The modalities examined included positive expiratory pressure (PEP) mask, forced expiratory technique (FET), exercise (EX), autogenic drainage (AD), and standard physical therapy (STD), consisting of postural drainage, percussion, and vibration. Computerized searches of the MEDLINE and Cumulative Index for Nursing and Allied Health databases were performed for the years from 1966 to 1993. The authors of relevant papers were contacted for unpublished information. Studies were considered relevant if they met the following criteria: randomized trials in patients with a definite diagnosis of CF; an intervention of any combination of PEP, FET, STD, AD, or EX; and an outcome of FEV1, sputum weight, or sputum clearance. A review of 456 citations yielded 65 potentially relevant trials and 8 review articles; of these, 35 met the inclusion criteria and were incorporated into the overview. These studies evaluated different combinations of physical therapy modalities; therefore, we performed seven separate meta-analyses comparing the independent techniques using the pooled effect size technique. Standard physical therapy resulted in a significantly greater sputum expectoration than no treatment (effect size of 0.61 SD units, p < 0.0001). The combination of standard therapy with EX with associated with a statistically significant increase in FEV1 over STD alone (effect size of 0.48 SD units, p = 0.04). No other differences between physical therapy modalities were found.

Cystic Fibrosis↗
PubMed1995

Strangulation of the colon complicating acute pancreatitis.

We report a patient with alcohol-induced necrotizing pancreatitis who developed a severe ileus followed by incarceration of a portion of the transverse colon within a ventral hernia. Laparotomy 9 days after the onset of symptoms revealed infarction of the transverse colon and infection of the pancreas. This is the first report of a case of acute pancreatitis that led to a strangulated ventral hernia of the colon. We believe that the enteric organisms that infected the pancreas originated in the incarcerated transverse colon.

Acute Disease↗